RESUMO
BACKGROUND: Skin adverse events associated with D-Penicillamine (DPA) are common and multi-faceted, although the presence of DPA or its metabolites has never been documented in the skin, because of inherent difficulties in determining its tissue levels. Thus, the association between DPA and DPA-related dermatoses has been only hypothesized on the basis of careful history, clinical observation and typical histopathological findings. OBJECTIVE: To detect DPA in biopsy specimens in a unique case of 25-year-late-onset elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum associated with a history of long-term high dose DPA, by applying a recently described analytical method to assess the presence of DPA in skin. METHODS: We used a reliable analytical method based on high-performance liquid chromatography coupled with amperometric detection to look for the presence of DPA in skin biopsy specimens. RESULTS: A chromatographic peak corresponding to DPA was evidenced in some affected skin samples collected from the patient. CONCLUSION: We documented the effective presence and the persistence after 25 years of DPA in the skin of a woman affected by elastotic cutaneous change due to a long-term therapy with DPA. This report provides further evidence of the relationship between DPA deposit in affected skin and clinical manifestation.
Assuntos
Quelantes/metabolismo , Degeneração Hepatolenticular/tratamento farmacológico , Penicilamina/metabolismo , Dermatopatias/induzido quimicamente , Quelantes/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Penicilamina/efeitos adversos , Penicilamina/uso terapêuticoRESUMO
The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences seem to affect the entire interaction between hyper-arousal, reduced hormonal response to stress and addiction severity. Our findings, although obtained in a small number of subjects, indicate a significant link between the perception of parental style/care/support during childhood and the ability to cope with stressful emotional stimuli in adulthood and addiction severity.
Assuntos
Nível de Alerta/fisiologia , Maus-Tratos Infantis/psicologia , Dependência de Heroína/complicações , Dependência de Heroína/psicologia , Transtornos do Humor/etiologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Análise de Variância , Criança , Pré-Escolar , Dependência de Heroína/sangue , Humanos , Hidrocortisona/sangue , Lactente , Modelos Lineares , Masculino , Transtornos do Humor/sangue , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto JovemRESUMO
New-generation antidepressants are a heterogeneous class of drugs used in the treatment of depression and related disorders. This review deals with the first new-generation antidepressant class to enter the pharmaceutical market, i.e., selective serotonin reuptake inhibitors (SSRIs), which are still the most prescribed and widely used ones. Their common characteristics are the comparable clinical efficacy, good tolerability and relative safety in comparison to "first generation antidepressants", i.e. classic tricyclic antidepressants and monoamine oxidase inhibitors. This class of drugs includes fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review, the main pharmacodynamic and pharmacokinetic properties of the six commercially available SSRIs are described, focusing on side and toxic effects, chemical-clinical correlations, interactions with other drugs, the role of therapeutic drug monitoring (TDM) and related bioanalytical methodologies.
Assuntos
Transtorno Depressivo/tratamento farmacológico , Monitoramento de Medicamentos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Benzofuranos/efeitos adversos , Benzofuranos/farmacocinética , Benzofuranos/uso terapêutico , Citalopram/efeitos adversos , Citalopram/farmacocinética , Citalopram/uso terapêutico , Transtorno Depressivo/metabolismo , Fluoxetina/efeitos adversos , Fluoxetina/farmacocinética , Fluoxetina/uso terapêutico , Fluvoxamina/efeitos adversos , Fluvoxamina/farmacocinética , Fluvoxamina/uso terapêutico , Humanos , Indóis/efeitos adversos , Indóis/farmacocinética , Indóis/uso terapêutico , Paroxetina/efeitos adversos , Paroxetina/farmacocinética , Paroxetina/uso terapêutico , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piperazinas/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Sertralina/efeitos adversos , Sertralina/farmacocinética , Sertralina/uso terapêutico , Cloridrato de VilazodonaRESUMO
Epidemiological and clinical data show frequent associations between adverse childhood experiences (ACEs) and substance abuse susceptibility particularly in adolescents. A large body of evidences suggests that the possible dysregulation of neuroendocrine responses as well as neurotransmitters function induced by childhood traumatic experiences and emotional neglect could constitute one of the essential biological changes implementing substance abuse vulnerability. Moreover, genotype variables and its environment interactions have been associated with an increased risk for early onset substance abuse. In this paper we present several data that support the hypothesis of the involvement of hypothalamus-pituitary-adrenal (HPA) axis in mediating the combined effect of early adverse experiences and gene variants affecting neurotransmission. The presented data also confirm the relationship between basal plasma levels of cortisol and ACTH, on the one hand, and retrospective measures of neglect during childhood on the other hand: the higher the mother and father neglect (CECA-Q) scores are, the higher the plasma levels of the two HPA hormones are. Furthermore, such positive relationship has been proved to be particularly effective and important when associated with the "S" promoter polymorphism of the gene encoding the 5-HTT transporter, both in homozygote and heterozygote individuals.
Assuntos
Maus-Tratos Infantis , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adaptação Psicológica , Adolescente , Fatores Etários , Criança , Pré-Escolar , Período Crítico Psicológico , Humanos , Sistemas Neurossecretores/fisiologia , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/fisiologia , Polimorfismo Genético , Resiliência Psicológica , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/fisiopatologiaRESUMO
The aim of the study was the development of analytical methods suitable for the quantification of L-dopa, carbidopa and entacapone in plasma of Parkinsonian patients treated with Stalevo(®). The metabolite 3-O-methyldopa was also determined to obtain some indications on the pharmacokinetics of L-dopa. For the simultaneous analysis of L-dopa, 3-O-methyldopa and carbidopa, a RP C18 column as the stationary phase and a mixture of methanol and a pH 2.88 phosphate buffer (8:92, v/v) as the mobile phase were used. A feasible plasma pre-treatment based on protein precipitation was implemented, obtaining extraction yield higher than 94% for all the analytes. For the analysis of entacapone a RP C8 column and a mixture of methanol, acetonitrile and a pH 1.90 phosphate buffer as the mobile phase (17.5:22.5:60, v/v/v) were used. A plasma pre-treatment procedure was developed, based on solid phase extraction of entacapone using Oasis HLB cartridges. Extraction yields were good, being always higher than 96%. Both methods, based on HPLC-ED (V=+0.8V), have been fully validated. Good linearity was obtained over the following concentration ranges: 100-4000 ng mL(-1) for L-dopa, 200-10,000 ng mL(-1) for 3-O-methyldopa, 25-4000 ng mL(-1) for carbidopa and 20-4000 ng mL(-1) for entacapone. Precision data were satisfactory, being R.S.D.% values lower than 5.64%; accuracy also resulted very good with recovery data higher than 90%. The proposed methods have been successfully applied to the analysis of patient plasma samples and seem to be suitable for therapeutic drug monitoring purposes.
Assuntos
Antiparkinsonianos/sangue , Antiparkinsonianos/uso terapêutico , Carbidopa/sangue , Catecóis/sangue , Catecóis/uso terapêutico , Levodopa/sangue , Metildopa/sangue , Nitrilas/sangue , Calibragem , Carbidopa/farmacocinética , Carbidopa/uso terapêutico , Catecóis/farmacocinética , Cromatografia Líquida de Alta Pressão , Combinação de Medicamentos , Humanos , Levodopa/farmacocinética , Levodopa/uso terapêutico , Metildopa/farmacocinética , Nitrilas/farmacocinética , Reprodutibilidade dos Testes , Extração em Fase SólidaRESUMO
A reliable chromatographic method for the determination of soy isoflavones (genistein, daidzein and glycitein) using a coulometric detection has been developed and applied to analyse plasma of postmenopausal women. The chromatographic separation was performed on a C18 reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. Coulometric detection was carried out at +0.500 V. A careful and rapid solid phase extraction procedure on hydrophilic/lipophilic cartridges was chosen for plasma sample purification with and without hydrolysis obtaining good extraction yield values for all the analytes (>90.0%). The enzymatic hydrolysis step was necessary for the determination of the total amount of soy isoflavones. The limit of quantitation was 0.5 ng mL(-1) for genistein and 0.25 ng mL(-1) for daidzein and glycitein. The method was found to be precise and accurate. Thus, the proposed method is suitable for the analysis of soy isoflavones (free and total amounts) in plasma of postmenopausal women under treatment with the SoymenGN dietary supplement.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Genisteína/sangue , Isoflavonas/sangue , Pós-Menopausa/sangue , Eletroquímica , Feminino , Humanos , Pessoa de Meia-Idade , Extração em Fase SólidaRESUMO
We used Flinder Sensitive Line (FSL) rats, a genetic model of unipolar depression, to examine whether changes in central GABAergic transmission are associated with a depressed phenotype. FSL rats showed an increased behavioral response to low doses of diazepam, as compared to either Sprague Dawley (SD) or Flinder Resistant Line (FRL) rats used as controls. Diazepam at a dose of 0.3 mg/kg, i.p., induced a robust impairment of motor coordination in FSL rats, but was virtually inactive in SD or FRL rats. The increased responsiveness of FSL rats was not due to changes in the brain levels of diazepam or its active metabolites, or to increases in the number or affinity of benzodiazepine recognition sites, as shown by the analysis of [(3)H]-flunitrazepam binding in the hippocampus, cerebral cortex or cerebellum. We therefore examined whether FSL rats differed from control rats for the expression levels of the K(+)/Cl(-) cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating the concentration gradient that allows Cl(-) influx through the anion channel associated with GABA(A) receptors. Combined immunoblot and immunohistochemical data showed a widespread increase in KCC2 expression in FSL rats, as compared with control rats. The increase was more prominent in the cerebellum, where KCC2 was largely expressed in the granular layer. These data raise the interesting possibility that a spontaneous depressive state in animals is associated with an amplified GABAergic transmission in the CNS resulting from an enhanced expression of KCC2.
Assuntos
Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Transtorno Depressivo/metabolismo , Hipocampo/metabolismo , Simportadores/metabolismo , Animais , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/farmacocinética , Fármacos do Sistema Nervoso Central/farmacologia , Cerebelo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Diazepam/administração & dosagem , Diazepam/farmacocinética , Diazepam/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Masculino , Destreza Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Especificidade da Espécie , Cotransportadores de K e Cl-RESUMO
Orphenadrine is an antimuscarinic agent mainly used for the treatment of parkinsonism and to alleviate the neuroleptic syndrome induced by antipsychotic drugs. A new, rapid analytical method, based on liquid chromatography with diode array detection (DAD), has been developed and applied to the determination of orphenadrine in plasma of schizophrenic patients for therapeutic drug monitoring and toxicological purposes. The chromatographic separation was performed on a pentafluorophenyl reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. DAD detection was carried out at 220 nm. A careful and rapid solid-phase extraction procedure on cyanopropyl cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for the analyte (>96.0%). The assays showed a linear response for orphenadrine (30-1000 ng mL(-1)). The method is also precise and selective. Thus, the method developed seems to be suitable for routine analysis of orphenadrine in psychiatric patients. Moreover, it was applied to plasma samples from a psychotic patient who had tried to poison himself with 1000 mg of orphenadrine and was undergoing polypharmacy.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/métodos , Antagonistas Muscarínicos/sangue , Orfenadrina/sangue , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Relação Dose-Resposta a Droga , Overdose de Drogas , Humanos , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/intoxicação , Síndrome Maligna Neuroléptica/tratamento farmacológico , Síndrome Maligna Neuroléptica/etiologia , Orfenadrina/administração & dosagem , Orfenadrina/intoxicação , Esquizofrenia/tratamento farmacológicoRESUMO
UNLABELLED: Childhood neglect and poor child-parent relationships have been reported to increase substance use disorders susceptibility. Stressful environmental factors, including emotional neglect, could affect individual personality traits and mental health, possibly inducing stable changes in hypothalamic-pituitary-adrenal (HPA) axis and brain mono-amine function, in turn involved in addictive behavior vulnerability. Therefore, we decided to investigate homovanillic (HVA) and prolactin (PRL) plasma levels, as expression of possible changes in dopamine function, ACTH and cortisol plasma levels, as measures of HPA axis function, and concomitant psychiatric symptoms profile in abstinent cocaine addicts, in relationship to their childhood history of neglect and poor parental care perception. METHODS: Fifty abstinent cocaine dependent patients, and 44 normal controls, matched for age and sex, were submitted to a detailed psychiatric assessment (DSM IV criteria). All patients and controls completed the Symptoms Check List-90 (SCL-90) and the Buss Durkee Hostility Inventory (BDHI), to evaluate psychiatric symptoms frequency and aggressiveness levels. The Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and Parental Bonding Instrument (PBI) have been used to retrospectively investigate parent-child relationships. Blood samples were collected to determine HVA, PRL, ACTH and cortisol basal plasma levels. RESULTS: Cocaine addicted individuals in general showed significantly lower HVA, and higher PRL, ACTH and cortisol basal levels respect to controls. In particular, neuroendocrine changes characterized cocaine addicts with childhood history of neglect and low perception of parental care. Obsessive-compulsive, depression and aggressiveness symptoms have been found related to poor parenting, inversely associated to HVA levels and directly associated to PRL, ACTH and cortisol levels. CONCLUSIONS: These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may partially contribute to a complex neurobiological derangement including HPA axis and dopamine system dysfunctions, playing a crucial role in addictive and affective disorders susceptibility.
Assuntos
Maus-Tratos Infantis , Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Mentais , Poder Familiar/psicologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Eletroquímica , Feminino , Ácido Homovanílico/sangue , Humanos , Hidrocortisona/sangue , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Personalidade , Prolactina/sangue , Análise de Regressão , Estudos Retrospectivos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) seems to be a risk condition for substance use disorders, possibly in relationship to common neurobiological changes, underlying both addictive and externalising behaviour susceptibility. Although this vulnerability has been primarily attributed to gene variants, previous studies suggest that also adverse childhood experiences may influence neurotransmission, affecting in particular brain dopamine (DA) system and possibly concurring to the development of behavioural disorders. Therefore, we decided to investigate ADHD symptoms and plasma concentrations of the DA metabolite homovanillic acid (HVA) in abstinent addicted patients, in comparison with healthy control subjects, evaluating whether ADHD scores were related with HVA levels, as expression of DA turnover, and whether HVA values, in turn, were associated with childhood emotional neglect. METHODS: Eighty-two abstinent drug dependent patients, and 44 normal controls, matched for age and sex, completed the Wender Utah Rating Scale (WURS), measuring ADHD symptoms, and the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Blood samples were collected to determine HVA plasma levels. RESULTS: Addicted individuals showed significantly higher ADHD scores and lower HVA levels respect to control subjects. ADHD scores at WURS in addicted patients negatively correlated with plasma HVA values. In turn, plasma HVA levels were inversely associated with childhood neglect measures, reaching statistical significance with "mother-antipathy" and "mother neglect" scores. CONCLUSIONS: These findings suggest the possibility that childhood experience of neglect and poor mother-child attachment may have an effect on central dopamine function as an adult, in turn contributing to both ADHD and substance abuse neurobiological vulnerability.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Maus-Tratos Infantis , Ácido Homovanílico/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Transtorno da Personalidade Antissocial/epidemiologia , Ansiedade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Maus-Tratos Infantis/psicologia , Comorbidade , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
A review with 103 references. Fluoxetine is the parent drug of the SSRI (selective serotonin reuptake inhibitor) antidepressant class, and is still one of the most highly used drugs of this class world-wide. Fluoxetine now has largely (albeit not completely) substituted older and less safe drugs such as tricyclic antidepressants. Different cytochrome P450 isoforms are involved in the metabolism of fluoxetine, however, the main active metabolite, norfluoxetine, is produced by the CYP2D6 action in the human liver. In this paper, the main metabolic characteristics of fluoxetine will be reviewed, with particular attention paid to the role of cytochrome isozymes. The pharmacological interactions of the drug will be overviewed, especially those concerning other drugs used in psychiatric clinics, such as antipsychotics and antidepressants and the relationships between pharmacological interactions and cytochrome activity will be discussed. Recently, much attention has been drawn to the therapeutic drug monitoring (TDM) of fluoxetine, and in particular to the analysis of fluoxetine enantiomers for which enantiomeric separations and enantioselective metabolism will also briefly be mentioned.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Fluoxetina/farmacologia , Fluoxetina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Animais , Interações Medicamentosas , Feminino , Humanos , Lactação/fisiologia , Gravidez , EstereoisomerismoRESUMO
A sensitive high-performance liquid chromatographic method has been developed for the determination of homovanillic acid (HVA), the main metabolite of dopamine, in human plasma. Analyses were carried out on a reversed-phase column (C8, 250 mm x 4.6 mm i.d., 5 microm) using a mobile phase composed of 10% methanol and 90% aqueous citrate buffer, containing octanesulfonic acid and EDTA at pH 4.8. Coulometric detection was used, setting the guard cell at +0.100 V, the first analytical cell at -0.200 V and the second analytical cell at +0.500 V. A careful solid-phase extraction procedure, based on strong anion exchange (SAX) cartridges (100 mg, 1 mL), was implemented for the pre-treatment of plasma samples. Extraction yield was satisfactory, being the mean value 98.0%. The calibration curve was linear over the concentration range of 0.2-25.0 ng mL(-1) of homovanillic acid. The limit of quantitation (LOQ) was 0.2 ng mL(-1) and the limit of detection (LOD) was 0.1 ng mL(-1). The method was successfully applied to plasma samples from former alcohol, cocaine and heroin addicts. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid in human plasma.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Homovanílico/sangue , Calibragem , Eletroquímica , Humanos , Sensibilidade e EspecificidadeRESUMO
Emblica officinalis Gaertn. is one of the most important plants of Ayurved, the traditional Indian medicine. In this ancient medicine, the fruit of Emblica officinalis is processed according to a method named "Svaras Bhavana", whereby the therapeutic potential of the plant is enhanced by treating the main herb with its own juice. For many years, the activity of the fruits was attributed to the high content of ascorbic acid; however, this has recently been questioned. The aim of the paper is to clarify this matter. A reliable and feasible HPLC method with diode array detection has been developed for the determination of ascorbic acid in Emblica fruit and particularly in Emblica fruit processed according to the Ayurvedic method. The antioxidant effects have also been evaluated in comparison to the real levels of Vitamin C by different antioxidant tests. The data obtained show that the Emblica fruit contains ascorbic acid (0.4%, w/w), and that the Ayurvedic method of processing increases the healthy characteristics of the fruit thanks to a higher antioxidant activity and a higher content of ascorbic acid (1.28%, w/w). It has also been found that Vitamin C accounts for approximately 45-70% of the antioxidant activity.
Assuntos
Antioxidantes/isolamento & purificação , Ácido Ascórbico/isolamento & purificação , Frutas , Ayurveda , Phyllanthus emblica , Antioxidantes/análise , Ácido Ascórbico/análise , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificaçãoRESUMO
A new fast capillary electrophoretic method has been developed for the analysis of the glycopeptide antibiotic vancomycin in formulations. An electrophoretic run is completed within 3.0 min; fused silica capillaries (100 microm i.d., 8.5 cm effective length and 48.5 cm total length) and a background electrolyte consisting of 12.5 mM, pH 2.5 phosphate buffer are used. The applied voltage is -20.0 kV; samples are injected by pressure (30 mbar x 3 s) at the anodic end of the capillary. The method was successfully applied to innovative controlled release microparticles consisting of a coated albumin core containing vancomycin. A simple procedure has been developed to obtain complete vancomycin extraction from microparticles using a 5% (w/v) sodium dodecyl sulphate aqueous solution. The method has been validated in terms of linearity, precision and accuracy. Good linearity was found in the 0.25-5.00 microg/mL range. Satisfactory precision was obtained, with relative standard deviation values always lower than 3.9%; accuracy was satisfactory, with recovery values between 97.8 and 102.2%. The method is also suitable for vancomycin determination in commercial capsules.
Assuntos
Antibacterianos/análise , Eletroforese Capilar/métodos , Vancomicina/análise , Cápsulas , Química Farmacêutica , Concentração de Íons de HidrogênioRESUMO
The present study investigated neuroendocrine and cardiovascular changes during experimentally-induced affective states in abstinent heroin-dependent subjects and healthy controls. The procedure for eliciting emotions in all subjects used pleasant and unpleasant stimuli that did not differ in subjective arousal properties. We investigated whether the valence of the stimuli differentially affected neuroendocrine responses by comparing neutral, pleasant and unpleasant pictures on heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), methyl-OH-phenyl-glycol (MHPG), norepinephrine (NE), epinephrine (EPI), adrenocorticotrophic hormone (ACTH) and cortisol (CORT) plasma levels. Twelve abstinent heroin-dependent subjects, in comparison with 12 control subjects, were submitted to three experimental sessions, each on one of three experimental days a week apart, in counterbalanced order: day 1=unpleasant pictures, day 2=pleasant pictures, day 3=neutral pictures. In the rating of subjective arousal pleasant and unpleasant stimuli received the same high score in comparison with neutral stimuli; a different cardiovascular and neuroendocrine pattern was obtained in healthy subjects: unpleasant stimuli elicited increases in HR, SBP, MHPG, NE, ACTH, CORT, whereas neutral and pleasant stimuli did not induce any significant response in hormonal levels. In contrast, in heroin addicts, despite increased perceptions of unpleasantness, HR, SBP, MHPG and NE levels did not increase after disliked stimuli; these subjects also reported increased arousal during exposure to neutral stimuli. In comparison with controls, addicted individuals showed higher CORT and ACTH basal levels, and a consequent lack of response to unpleasant stimuli. The results indicate that neuroendocrine and cardiovascular systems respond selectively to affective, motivationally relevant stimuli, and that substance use disorders may be associated with dysregulation of emotion-processing mechanisms.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Emoções/fisiologia , Dependência de Heroína/sangue , Dependência de Heroína/psicologia , Hidrocortisona/sangue , Adulto , Análise de Variância , Humanos , Masculino , Sistemas Neurossecretores/metabolismo , Transtornos Relacionados ao Uso de Opioides/sangue , Transtornos Relacionados ao Uso de Opioides/psicologiaRESUMO
A method based on high-performance liquid chromatography with UV detection in combination with solid-phase extraction for sample pretreatment has been developed for the simultaneous analysis of the antiepileptic drug oxcarbazepine and its main metabolites in human plasma. The extraction of the analytes from plasma samples was carried out by means of a selective solid-phase extraction procedure using hydrophilic-lipophilic balance cartridges. The separation was obtained on a reversed-phase column (C(18), 150x4.6 mm I.D., 5 micrometer) using a phosphate buffer-acetonitrile-methanol-triethylamine mixture (final apparent pH* 3.5) as the mobile phase. Under these chromatographic conditions, oxcarbazepine and its metabolites 10,11-dihydro-10-hydroxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine and the internal standard are baseline separated in less than 9 min. The extraction yield values were >94% for all analytes and the precision, expressed by the RSD%, was in the low percentage range. For the entire method, including sample pre-treatment and HPLC determination, the linearity of the calibration lines, expressed by the linear correlation coefficient, was better than 0.995; the limit of quantitation was 15 ng ml(-1). The method was applied to plasma samples from patients undergoing chronic treatment with oxcarbazepine, both in monotherapy and in polytherapy. Based on the analytical parameters precision, accuracy, limit of quantitation and analysis time the method is suitable for routine application in therapeutic drug monitoring.
Assuntos
Anticonvulsivantes/sangue , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Epilepsia/sangue , Espectrofotometria Ultravioleta/métodos , Humanos , Oxcarbazepina , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A precise and feasible high-performance liquid chromatographic (HPLC) method for the analysis of the novel antipsychotic drug quetiapine in plasma has been developed. The analysis was carried out on a C8 (150x4.6 mm i.d., 5 micrometer) reversed-phase column, using a mixture of acetonitrile, methanol and pH 1.9 phosphate buffer as the mobile phase; triprolidine was used as the internal standard. Careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE). A good linearity was found in the 4-400 ng ml(-1) quetiapine plasma concentration range. The application to some plasma samples of patients treated with Seroquel(R) tablets gave satisfactory results. The accuracy was good (quetiapine mean recovery=92%), as well as the precision (mean RSD=3.3%). The method seems to be suitable for the clinical monitoring of patients treated with quetiapine.
Assuntos
Antipsicóticos/sangue , Dibenzotiazepinas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Fumarato de QuetiapinaRESUMO
Two different analytical methods for the quality control of fluoxetine in commercial formulations have been developed and compared: a spectrofluorimetric method and a capillary zone electrophoretic (CZE) method. The fluorescence emission values were measured at lambda=293 nm when exciting at lambda=230 nm. The CZE method used an uncoated fused-silica capillary and pH 2.5 phosphate buffer as the background electrolyte. The extraction of fluoxetine from the capsules consisted of a simple one-step dissolution with methanol/water, filtration and dilution. Both methods gave satisfactory results in terms of precision; the best results were obtained for the electrophoretic method, with RSD% values always lower than 2.0%. The accuracy was assessed by means of recovery studies, which gave very good results, between 97.5 and 102.6%. Furthermore, both methods also have the advantage of being very rapid.
Assuntos
Fluoxetina/análise , Cápsulas , Eletroforese Capilar , Reprodutibilidade dos Testes , Espectrometria de FluorescênciaRESUMO
In the last few years, new drugs for the treatment of schizophrenia have been introduced in therapy which have noticeably improved the quality of life of many schizophrenic patients. These new "atypical" drugs have chemical, pharmacological and clinical properties which are different from those of the classical neuroleptics. The most used drugs among the "atypical" antipsychotics are clozapine, olanzapine, quetiapine and risperidone. Despite several differences in their pharmacokinetic and pharmacodynamic profiles, they show some common properties: e.g. they don't cause extrapyramidal side effects, and they are active against the negative as well as positive symptoms of schizophrenia. The need for clinical monitoring of patients undergoing therapy is still evident because the onset of side effects is often related to high plasma concentrations of the drug. The clinical monitoring of patients can significantly improve the knowledge of pharmacological interactions among different CNS drugs, as well as enhance the compliance of the patients, thus leading to higher treatment efficacy. In order to carry out efficient clinical monitoring, reliable analytical methods are needed to determine the analytes even at very low concentrations and in the presence of other drugs. For this purpose, analytical techniques such as gas or liquid chromatography are often used coupled with sensitive and selective means of detection, such as fluorimetric, electrochemical or mass spectrometry detectors. The most recent studies on the determination of atypical antipsychotics will be reviewed in addition to the issue of sample pretreatment which is a critical step when the analysis of biological fluids is concerned.
Assuntos
Antipsicóticos/análise , Monitoramento de Medicamentos/métodos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Humanos , Cooperação do Paciente , Esquizofrenia/sangueRESUMO
The recent antidepressant drug reboxetine was quantified in pharmaceutical tablets by derivative spectrophotometry and capillary zone electrophoresis. The feasible sample pretreatment consists of a single extraction with a pH 2.5 phosphate buffer, centrifugation and dilution. For the spectrophotometric assay, the fourth derivative of the absorbance was used which gave satisfactory results in terms of accuracy (mean recovery 99.7%) and precision (mean RSD 3.4%). The electrophoretic experiments were carried out using the shortest effective length of the capillary (8.5 cm) in order to obtain a very rapid separation of reboxetine and dibenzepine used as the internal standard. Using a pH 2.5, 50 mM phosphate buffer as the background electrolyte, each analysis lasted less than 2.5 min. Accuracy (101.3%) and precision (1.5%) were very good.